Cutaneous aging results from both intrinsic chronological aging and extrinsic sun-exposure. Montagna et al., J. Am. Acad. Dermatol. 1989, 21:907-918; Kligman, L. H., Aging and the Skin. Raven Press, New York, 1989, pp. 331-346; Taylor et al., J. Am. Acad. Dermatol. 1990, 221:1-15. The majority of changes associated with an aged appearance result from chronic sun-damage. Warren et al., J. Am. Acad. Dermatol. 1991, 25:751-760; Frances, C. and Robert, L., Int. J. Dermatol. 1984, 23:166-179. Dramatic alterations of the superficial dermis accompany the deep wrinkles and laxity common in photoaged skin. The major histopathologic alteration of photoaged skin is the accumulation of material which, on routine histopathologic examination, has the staining characteristics of elastin and is, thus, termed solar elastosis. Immunohistochemical staining has shown the poorly-formed fibers comprising solar elastosis to be composed of elastin (Chen et al., J. Invest. Dermatol. 1986, 87:334-337; Mera et al., Br. J. Dermatol. 1987, 117:21-27) fibrillin (Chen et al., J. Invest. Dermatol. 1986, 87:334-337; Dahlback et al., J. Invest. Dermatol. 1990, 94:284-291; Bernstein et al., J. Invest. Dermatol. 1994, 103:182-186) and versican, the normal components of elastic fibers (Zimmerman et al., J. Cell. Biol. 1994, 124:817-825). A coordinate increase in elastin, fibrillin and versican mRNAs has been demonstrated in fibroblasts derived from photodamaged skin, as compared to fibroblasts derived from normal skin from the same individuals. Bernstein et al., J. Invest. Dermatol. 1994, 103:182-186. Elevated elastin mRNA levels in sun-damaged skin result from enhanced elastin promoter activity, as shown by transient transfections of fibroblasts with a DNA construct composed of the human elastin promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Bernstein et al., J. Invest. Dermatol. 1994, 103:182-186.
A transgenic mouse line which expresses the human elastin promoter/CAT construct has now been developed to further study the role of elastin promoter activation in cutaneous photoaging. These mice express human elastin promoter activity in a tissue-specific and developmentally regulated manner. Promoter activity can be studied in this model as a function of small increases in ultraviolet radiation, demonstrating the sensitivity of the assay. In addition quantitative data can be obtained after only a single exposure to ultraviolet radiation. This transgenic mouse and fibroblasts derived from this mouse are useful as in vivo and in vitro models to study cutaneous photoaging and in the identification of agents which may protect against photodamage.